NM_004688.3:c.178-10T>C

Variant names:

• chr2-151279000-A-G
• rs289831
• NM_004688.3:c.178-10T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_004688.3(NMI):​c.178-10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 1,543,842 control chromosomes in the GnomAD database, including 17,070 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.19 (3768 hom., cov: 32)
  • Exomes 𝑓: 0.13 (13302 hom.)
• Consequence: NMI NM_004688.3 intron
• Scores: Splicing: ADA: 0.004861
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.10
• Publications: 16 publications found

Genes affected

NMI (HGNC:7854): (N-myc and STAT interactor) NMYC interactor (NMI) encodes a protein that interacts with NMYC and CMYC (two members of the oncogene Myc family), and other transcription factors containing a Zip, HLH, or HLH-Zip motif. The NMI protein also interacts with all STATs except STAT2 and augments STAT-mediated transcription in response to cytokines IL2 and IFN-gamma. The NMI mRNA has low expression levels in all human fetal and adult tissues tested except brain and has high expression in cancer cell line-myeloid leukemias. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004688.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NMI	NM_004688.3	MANE Select	c.178-10T>C		intron	N/A	NP_004679.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NMI	ENST00000243346.10	TSL:1 MANE Select	c.178-10T>C		intron	N/A	ENSP00000243346.5
	NMI	ENST00000491771.5	TSL:2	n.359-10T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28868 AN: 152050 Hom.: 3763 Cov.: 32

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.0577

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.181

GnomAD2 exomes AF: 0.137 AC: 32045 AN: 233598 AF XY: 0.138

Gnomad AFR exome AF: 0.368

Gnomad AMR exome AF: 0.0852

Gnomad ASJ exome AF: 0.168

Gnomad EAS exome AF: 0.128

Gnomad FIN exome AF: 0.0594

Gnomad NFE exome AF: 0.117

Gnomad OTH exome AF: 0.129

GnomAD4 exome AF: 0.127 AC: 176519 AN: 1391674 Hom.: 13302 Cov.: 23 AF XY: 0.129 AC XY: 89325 AN XY: 690870

African (AFR) AF: 0.368 AC: 11529 AN: 31364

American (AMR) AF: 0.0893 AC: 3667 AN: 41058

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 4225 AN: 25212

East Asian (EAS) AF: 0.123 AC: 4803 AN: 38892

South Asian (SAS) AF: 0.199 AC: 16224 AN: 81722

European-Finnish (FIN) AF: 0.0635 AC: 3296 AN: 51924

Middle Eastern (MID) AF: 0.237 AC: 1310 AN: 5532

European-Non Finnish (NFE) AF: 0.116 AC: 122901 AN: 1058302

Other (OTH) AF: 0.149 AC: 8564 AN: 57668

GnomAD4 genome AF: 0.190 AC: 28908 AN: 152168 Hom.: 3768 Cov.: 32 AF XY: 0.186 AC XY: 13820 AN XY: 74406

African (AFR) AF: 0.368 AC: 15257 AN: 41476

American (AMR) AF: 0.138 AC: 2114 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 588 AN: 3470

East Asian (EAS) AF: 0.127 AC: 658 AN: 5176

South Asian (SAS) AF: 0.201 AC: 968 AN: 4826

European-Finnish (FIN) AF: 0.0577 AC: 612 AN: 10614

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8205 AN: 68008

Other (OTH) AF: 0.179 AC: 378 AN: 2112

Alfa AF: 0.141 Hom.: 1071

Bravo AF: 0.200

Asia WGS AF: 0.188 AC: 654 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	18
DANN	Benign	0.79
PhyloP100		2.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0049
dbscSNV1_RF	Benign	0.23
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs289831; hg19: chr2-152135514; COSMIC: COSV54638308; COSMIC: COSV54638308;